Arthroplasty, Replacement, KneePhase 2AXIOMATIC-TKRNCT03891524
A Study of JNJ-70033093 (BMS-986177) Versus Subcutaneous Enoxaparin in Participants Undergoing Elective Total Knee Replacement Surgery
A Phase 2 study testing JNJ-70033093 25 mg, JNJ-70033093 50 mg and JNJ-70033093 100 mg in people with Arthroplasty, Replacement, Knee, run by Janssen Research & Development, LLC at 117 sites in 18 countries.
Trial summary
The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis [DVT] [asymptomatic confirmed by venography assessment or objectively confirmed symptomatic], nonfatal pulmonary embolism [PE], or any death)… Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Arthroplasty, Replacement, Knee
- What is being tested?
- JNJ-70033093 25 mg, JNJ-70033093 50 mg and JNJ-70033093 100 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,242 participants
- Where
- 117 sitesin 18 countries
- Study dates
- 17 Jun 2019to 6 Apr 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery
- Medically stable and appropriate for anticoagulant prophylaxis on the basis of clinical laboratory tests performed as part of local standard-of-care as part of screening for elective TKR surgery
- Has plans to undergo an elective primary unilateral TKR surgery
- A woman must be- a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than [<]1 percent [%] per year when used consistently and correctly) and agrees to remain on a highly effective method for the duration of study drug with JNJ-70033093 plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 34 days after the completion of treatment, pregnancy testing (serum or urine) prior to the first dose of study drug
- Willing and able to adhere to the lifestyle restrictions specified in this protocol
Who cannot join
- History of any condition for which the use of low molecular-weight heparin (LMWH) is not recommended in the opinion of the investigator (for example, previous allergic reaction, creatinine clearance <30 milliliter per minute [mL/minute])
- History of severe hepatic impairment
- Planned bilateral revision or unicompartmental procedure
- Unable to undergo venography (for example, due to contrast agent allergy, poor venous access, or impaired renal function that would increase the risk of contrast-induced nephropathy
- Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity
Trial locations and contacts
117 sites in 18 countries.
117 sites in 18 countries
Japan15 sites
Matsudo City General Hospital
Chiba, 270-2296
Hakodate Goryoukaku Hospital
Hakodate, 040 8611
Japanese Red Cross Hamamatsu Hospital
Hamamatsu, 434-8533
Itami City Hospital
Itami-shi, 664-8540
Yonemori Hospital
Kagoshima, 890-0062
Japan Community Health care Organization Kyushu Hospital
Kitakyushu-shi, 806-8501
Marunouchi Hospital
Matsumoto, 390-8601
Chubu Rosai Hospital
Nagoya, 455-8530
Juntendo University Nerima Hospital
Nerima-Ku, 177-8521
National Hospital Organization Okayama Medical Center
Okayama, 701-1192
Yuuai Medical Center
Okinawa, 901-0224
Japan Community Health Care Organization Saitama Medical Center
Saitama, 350-8550
Saitama City Hospital
Saitama-shi, 336-8522
Nagano Prefectural Shinshu Medical Center
Suzaka, 386-8610
Juntendo University Hospital
Tokyo, 113-8431
Spain11 sites
Hosp. Univ. Fundacion Alcorcon
Alcorcón, 28922
Hosp. Univ. Germans Trias I Pujol
Badalona, 08916
Hosp Clinic de Barcelona
Barcelona, 08036
Hosp. Univ. de Bellvitge
Barcelona, 08907
Hosp Univ Vall D Hebron
Barcelona, 8035
Complejo Hospitalario de Jaen
Jaén, 23007
Hosp. Univ. 12 de Octubre
Madrid, 28041
Hosp. Univ. La Paz
Madrid, 28046
Corporacio Sanitari Parc Tauli
Sabadell, 08208
Hosp. Clinico Univ. de Valencia
Valencia, 46010
Hosp. Univ. I Politecni La Fe
Valencia, 46026
United States9 sites
Central Research Associates, Inc.
Birmingham, Alabama, 35205
Denver Metro Orthopedics, PC
Englewood, Colorado, 80113
Memorial Hermann Memorial City Medical Center
Houston, Texas, 77024
Bowen Hefley Orthopedics
Little Rock, Arkansas, 72205
Arizona Research Center
Phoenix, Arizona, 85053
DMI Research
Pinellas Park, Florida, 33782
Gulfcoast Research Institute
Sarasota, Florida, 34232
University Orthopedic and Joint Replacement Center
Tamarac, Florida, 33321
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, 90502
Poland9 sites
Samodzielny Publiczny Zaklad Opieki Zdrowotnej w Bielsku Podlaskim Oddzial Urazowo Ortopedyczny
Bielsk Podlaski, 17 100
Szpital Ogolny im. W. Ginela, Oddzial Urazowo-Ortopedyczny
Grajewo, 19-200
Wojewodzki Szpital Zespolony w Kielcach, Klinika Chirurgii Ortopedyczno-Urazowej
Kielce, 25-001
Oddzial Ortopedii i Traumatologii Narzadu Ruchu Szpital Specjalistyczny im Ludwika Rydygiera
Krakow, 31 826
CSK UM Klinika Ortopedii
Lodz, 92-213
Oddzial Urazowo-Ortopedyczny Wojewodzki Szpital Specjalistyczny
Lublin, 20-718
Oddzial Ortopedii Specjalistyczny Szpital im. E.Szczeklika
Tarnów, 33-100
Oddzial Chirurgii Urazowej iOrtopedycznej Wojewodzki Szpital Brodnowski SPZOZ
Warsaw, 03 242
Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
Wroclaw, 50 556
Hungary8 sites
Semmelweis Egyetem
Budapest, 1085
Debreceni Egyetem
Debrecen, 4032
Petz Aladar Megyei Oktato Korhaz
Gyõr, 9023
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvár, 7400
Bacs-kiskun Megyei Korhaz
Kecskemét, 6000
Szegedi Tudomanyegyetem
Szeged, 6725
Fejer Varmegyei Szent Gyorgy Egyetemi Oktatokorhaz
Székesfehérvár, 8000
MAV Korhaz es Rendelointezet
Szolnok, 5000
Argentina7 sites
Hospital Britanico de Buenos Aires
Buenos Aires, C1280AEB
Clinica Adventista Belgrano
CABA, C1430EGF
Hospital San Roque
Córdoba, 5000
Clínica Chutro
Córdoba, X5000EPU
Hospital Italiano La Plata
La Plata, B1900AXI
Instituto de Investigaciones Clinicas Rosario
Rosario, S2000BIF
Sanatorio Corporación Médica de General San Martín
San Martin, B1650BNB
Russia7 sites
National Medical Research Center of Traumatology and Orthopaedics n.a. G.A. Ilizarov
Kurgan, 640014
Private Healthcare Institution 'Clinical Hospital 'RZD-Medcine' n.a. N.A.Semashko'
Moscow, 109386
Privolzhsky Regional Medical Center of Federal Medical and Biological Agency
Nizhny Novgorod, 603137
National medical research center of Traumatology and Orthopaedics n.a. R.R.Vreden
Saint Petersburg, 195427
State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin
Samara, 443095
Smolensk Federal Center of Traumatology, Orthopedics and Endoprothesis Replacement
Smolensk, 214031
Sochi City Hospital #4
Sochi, 354057
Turkey (Türkiye)7 sites
Adana City Hospital
Adana, 01060
Diskapi Yildırim Beyazid Training and Research Hospital
Ankara, 06110
Yıldırım Beyazıt University Yenimahalle Training and Research Hospital
Ankara, 06370
Antalya Training And Research Hospital
Antalya, 07100
Bakirkoy Training and Research Hospital
Istanbul, 34147
Sisli Etfal Research Training Hospital
Istanbul, 34371
Izmir Tepecik Training and Research Hospital
Izmir, 35180
Ukraine7 sites
Ivano-Frankivsk Regional Clinical Hospital
Ivano-Frankivsk, 76008
Institute of Spine and JointPathology named after Prof.Sytenko of NationalAcademy of MedicalSciences
Kharkiv, 61024
Municipal Institution of Health Care 'Kharkiv Regional Clinical Traumatology Hospital'
Kharkiv, 61176
Kyiv Regional Clinical Hospital
Kyiv, 04107
Communal Institution of Lviv Regional Council 'Lypa Lviv Regional Hospital'
Lviv-Vynnyky, 79495
Municipal Non-profit Enterprise 'Odesa Regional Clinical Hospital' Odesa Regional Council
Odesa, 65025
Vinnytsya Regional Clinical Hospital named after M.I.Pirogov
Vinnytsia, 21018
Italy6 sites
Cliniche Humanitas Gavazzeni
Bergamo, 24125
Azienda Ospedaliera Papa Giovanni XXIII
Bergamo, 24127
Istituto Ortopedico Rizzoli
Bologna, 40136
Policlinico S. Matteo
Pavia, 27100
Istituto Clinico Humanitas
Rozzano, 20089
A.O.U. Città della Salute e della Scienza
Torino, 10126
Bulgaria5 sites
University Multiprofile Hospital for Active Treatment Dr. Georgi Stranski
Pleven, 5800
Acibadem City Clinic Tokuda Hospital
Sofa, 1407
University Multiprofile Hospital Sofiamed Sofia
Sofia, 1330
MHAT Tzaritza Joanna
Sofia, 1527
Medical Center - Medical Complex BEROE EOOD
Stara Zagora, 6000
Portugal5 sites
Centro Hospitalar do Baixo Vouga - Hospital Infante Dom Pedro
Aveiro, 3810-501
Hosp de Cascais
Cascais, 2755-009
H. Santo António - Centro Hospitalar do Porto
Porto, 4099-001
CHS - Hosp. Orto. Sant'Iago do Outao
Setúbal, 2900-180
ULSAM, EPE - Hospital de Santa Luzia
Viana do Castelo, 4904-858
Belgium4 sites
ZNA Middelheim
Antwerp, 2020
Ziekenhuis Oost-Limburg
Genk, 3600
Jessa Ziekenhuis
Hasselt, 3500
ZNA Jan Palfijn
Merksem, 2170
Canada4 sites
Lakeridge Health
Ajax, Ontario, L1S 2J4
Hamilton Health Sciences Corporation
Hamilton, Ontario, L8V1C3
The Ottawa Hospital Research Institute
Ottawa, Ontario, K1H 8L6
Medical Investigative and Clinical Evaluation Inc
Windsor, Ontario, N8W 1E6
Greece4 sites
General Hospital of Attiki 'KAT'
Kifissia, 14561
General Hospital of Nea Ionia 'Konstantopoulio'
Nea Ionia, 14233
University General Hospital of Rio Patras
Pátrai, 26504
Papageorgiou General Hospital
Thessaloniki, 56403
Israel4 sites
Rambam Medical Center
Haifa, 31096
Carmel Medical Center
Haifa, 34362
Meir Medical Center
Kfar Saba, 44281
Kaplan Medical Center
Rehovot, 7610001
Brazil3 sites
Hospital Sao Francisco de Assis
Belo Horizonte, 30360-290
Hospital e Maternidade Dr Christovao da Gama S.A
Santo André, 09030-010
Hospital Estadual Mario covas
Santo André, 09190-615
South Africa2 sites
Steve Biko Academic Hospital
Pretoria, 0001
Clinical Project Research SA
Worcester, 6850
About this study
Official title: A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093 (BMS-986177), an Oral Factor XIa Inhibitor, Versus Subcutaneous Enoxaparin in Subjects Undergoing Elective Total Knee Replacement Surgery
The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis [DVT] [asymptomatic confirmed by venography assessment or objectively confirmed symptomatic], nonfatal pulmonary embolism [PE], or any death) during the treatment period.
Read the detailed description
JNJ-70033093 is an oral anticoagulant for prevention and treatment of thromboembolic events (for example, VTE) that binds and inhibits activated form of human coagulation Factor XI (FXIa) with high affinity and selectivity. The study will consist of 3 phases: up to 30-day screening phase before total knee replacement (TKR) surgery, 10 to14 day postoperative dosing phase, and 4-week follow-up phase. The hypothesis of this study is JNJ-70033093 reduces risk of total VTE during treatment period. The total duration of participation following randomization will be approximately 6 weeks. Efficacy evaluations include unilateral venography assessment of operated leg and assessments of symptomatic DVT, PE, or death. Safety evaluation includes adverse events, clinical laboratory tests, and physical examinations. The safety and efficacy will be monitored throughout the study.
- Conditions
- Arthroplasty, Replacement, Knee
- Being tested
- JNJ-70033093 25 mg, JNJ-70033093 50 mg, JNJ-70033093 100 mg, JNJ-70033093 200 mg, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
JNJ-70033093 25 mgDrug
Also called BMS-986177
Participants will receive JNJ-70033093 25 mg (1*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days.
JNJ-70033093 50 mgDrug
Also called BMS-986177
Participants will receive JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days.
JNJ-70033093 100 mgDrug
Also called BMS-986177
Participants will receive JNJ-70033093 100 mg (1*100 mg capsule) BID, orally for 10 to 14 postoperative days.
JNJ-70033093 200 mgDrug
Also called BMS-986177
Participants will receive JNJ-70033093 200 mg (2*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days.
PlaceboDrug
Participants will receive placebo matching to JNJ-70033093, orally.
Enoxaparin 40 mgDrug
Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days.
| Study group | Role | What they receive |
|---|---|---|
| Group A: JNJ-70033093 25 mg + Placebo BID | Experimental | Participants will receive JNJ-70033093 25 milligram (mg) (1*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days. Receives: Drug: JNJ-70033093 25 mg; Drug: Placebo |
| Group B: JNJ-70033093 50 mg BID | Experimental | Participants will receive JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days. Receives: Drug: JNJ-70033093 50 mg |
| Group C: JNJ-70033093 100 mg + Placebo BID | Experimental | Participants will receive JNJ-70033093 100 mg (1*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days. Receives: Drug: JNJ-70033093 100 mg; Drug: Placebo |
| Group D: JNJ-70033093 200 mg BID | Experimental | Participants will receive JNJ-70033093 200 mg (2*100 mg capsules) BID orally for 10 to 14 postoperative days. Receives: Drug: JNJ-70033093 200 mg |
| Group E: JNJ-70033093 25 mg Once Daily + Placebo | Experimental | Participants will receive JNJ-70033093 25 mg (1*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. Receives: Drug: JNJ-70033093 25 mg; Drug: Placebo |
| Group F: JNJ-70033093 200 mg Once Daily + Placebo | Experimental | Participants will receive JNJ-70033093 200 mg (2*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. Receives: Drug: JNJ-70033093 200 mg; Drug: Placebo |
| Group G: JNJ-70033093 50 mg once daily + Placebo | Experimental | Participants will receive JNJ-70033093 50 mg (2*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. Receives: Drug: JNJ-70033093 50 mg; Drug: Placebo |
| Group I: Enoxaparin 40 mg Once Daily | Active comparator | Participants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days. Receives: Drug: Enoxaparin 40 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death.
Measured: Up to Day 14
Secondary outcomes (29)
Number of Participants With Any Bleeding Event (CEC-adjudicated)
Any bleeding was defined as the composite of major bleeding according to the International Society on Thrombosis and Haemostasis (ISTH) criteria modified for the surgical setting, clinically relevant nonmajor bleeding events, or minimal bleeding events as assessed by the CEC.
Measured: Up to Day 14; Up to Day 52
Number of Participants With Total VTE (CEC-adjudicated)
Total VTE was defined as the composite of (CEC-adjudicated) proximal and/or DVT (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal PE, or any death.
Measured: Up to Day 52
Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated)
Composite of Major bleeding event (BE): Fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hemoglobin (Hb) level of 20 grams per liter (g/L) or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; surgical site bleeding that requires second intervention open, arthroscopic, endovascular,or hemarthrosis resulting in prolonged hospitalization, deep wound infection and/or either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: Epistaxis, Gastrointestinal bleed,Hematuria,Bruising/ecchymosis,Hemoptysis,Hematoma.
Measured: Up to Day 14, Up to Day 52
Number of Participants With Major Bleeding Events (CEC-adjudicated)
Number of participants with major BE (adjudicated by CEC) were reported. Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability.
Measured: Up to Day 14; Up to Day 52
Number of Participants With CRNM Bleeding Events (CEC-adjudicated)
Number of participants with CRNM bleeding events (adjudicated by CEC) were reported. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Measured: Up to Day 14; Up to Day 52
Number of Participants With Minimal Bleeding Events (CEC-adjudicated)
Number of participants with minimal bleeding events (adjudicated by CEC) were reported. Minimal bleeding event was defined as any bleeding event not met major or CRNM criteria. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Measured: Up to Day 14; Up to Day 52
Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated)
Major Bleeding events were defined as: fatal bleeding; bleeding that is symptomatic and occurs in critical area/organ and/or; extrasurgical site bleeding causing fall in Hb level of 20 g/L or more, or leading to transfusion of 2 or more units of whole blood or red cells with temporal association within 24-48 hours to bleeding, and/or; requires second intervention open, arthroscopic, endovascular, or hemarthrosis resulting in prolonged hospitalization or a deep wound infection and/or; either unexpected and prolonged and/or sufficiently large to cause hemodynamic instability. CRNM bleeding: acute clinically overt bleeding that does not satisfy additional criteria required for bleeding event to be defined as major BE is still considered clinically relevant for example: epistaxis, gastrointestinal bleed, hematuria, bruising/ecchymosis, hemoptysis, hematoma.
Measured: Up to Day 14; Up to Day 52
Number of Participants With Major VTE (CEC-adjudicated)
Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death.
Measured: Up to Day 52
Number of Participants With Major VTE (CEC-adjudicated)
Number of participants with major VTE (adjudicated by CEC) were reported. Major VTE was defined as a composite of proximal DVT (asymptomatic confirmed by venography or objectively confirmed symptomatic), nonfatal PE, or any death.
Measured: Up to Day 14
Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
Number of participants with proximal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Measured: Up to Day 14
Number of Participants With Proximal DVT (CEC-adjudicated)
Number of participants with proximal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Measured: Up to Day 52
Number of Participants With Distal DVT (CEC-adjudicated)
Number of participants with distal DVT (CEC-adjudicated) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Measured: Up to Day 14
Number of Participants With Distal DVT (CEC-adjudicated)
Number of participants with distal DVT (adjudicated by CEC) were reported. DVT asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic.
Measured: Up to Day 52
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Number of participants with nonfatal PE (adjudicated by CEC) were reported.
Measured: Up to Day 14
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Number of participants with nonfatal PE (adjudicated by CEC) were reported.
Measured: Up to Day 52
Number of Participants With Deaths (CEC-adjudicated)
Number of participants with deaths (CEC-adjudicated) were reported.
Measured: Up to Day 14
Number of Participants With Deaths (CEC-adjudicated)
Number of participants with deaths (CEC-adjudicated) were reported.
Measured: Up to Day 52
Apparent Clearance (CL/F) of JNJ-70033093
Apparent clearance of a drug was defined as a measure of the rate at which a drug got metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Measured: Up to Day 14
Apparent Volume of Distribution (V/F) of JNJ-70033093
V/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug.
Measured: Up to Day 14
Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex
Impact of demographic character (sex) on CL/F was assessed.
Measured: Up to Day 14
Impact of Selected Demographic: Age on CL/F
Impact of age on CL/F was assessed.
Measured: Up to Day 14
Impact of Selected Demographic: Weight on CL/F
Impact of weight on CL/F was assessed.
Measured: Up to Day 14
Impact of Selected Laboratory Values: Renal Function on CL/F
Impact of renal function on CL/F was assessed. The outcome measure was reported based on CRCL.
Measured: Up to Day 14
Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F)
Impact of sex on V/F was assessed.
Measured: Up to Day 14
Impact of Selected Demographics : Age on V/F
Impact of age on V/F was assessed.
Measured: Up to Day 14
Impact of Selected Demographics : Weight on V/F
Impact of weight on V/F was assessed.
Measured: Up to Day 14
Impact of Selected Laboratory Values: Renal Function on V/F
Impact of renal function on V/F was assessed. The outcome measure is reported based on CRCL.
Measured: Up to Day 14
Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach
The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
Measured: Up to 14 days
Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach
The dose-response trend test based on the MCP-Mod framework consisted of contrast tests defined by prespecified candidate models (4 Emax dose-response models with varying degrees of ED50). Each model was evaluated for significance of trend, based on its optimal contrast, resulting in four t-test statistics, one for each candidate model. The t-test statistics were adjusted for the fact that 4 candidate models were included in the trend testing. The dose response of the drug was then established if the maximum of the t-test statistics exceeded the 95th percentile critical value. Here 'number' signifies the estimated response rate.
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2019
- Study start17 Jun 2019
- Primary completion6 Apr 2021
- Study completion6 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Arthroplasty, Replacement, KneeStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 1,242 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03891524
- Sponsor's protocol ID
- CR108600
- Other IDs
- 70033093THR2001, 2018-004237-32, 2018
- Acronym
- AXIOMATIC-TKR
- Status last verified
- Mar 2025
- First submitted
- 25 Mar 2019
- Last updated
- 30 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Publications
Whiteson HZ, Frishman WH. Factor XI/XIa Inhibitors: A New Approach to Anticoagulation. Cardiol Rev. 2025 Jul-Aug 01;33(4):306-311. doi: 10.1097/CRD.0000000000000624. Epub 2023 Dec 1.
PubMed 38038437Weitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, Mahaffey KW, Notani RS, Roberts R, Segers A, Raskob GE; AXIOMATIC-TKR Investigators. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021 Dec 2;385(23):2161-2172. doi: 10.1056/NEJMoa2113194. Epub 2021 Nov 15.
PubMed 34780683
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093 (BMS-986177), an Oral Factor XIa Inhibitor, Versus Subcutaneous Enoxaparin in Subjects Undergoing Elective Total Knee Replacement Surgery
- ClinicalTrials.gov ID
- NCT03891524
- Acronym / sponsor ID
- AXIOMATIC-TKR / CR108600
- Conditions
- Arthroplasty, Replacement, Knee
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,242 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 17 Jun 2019 (actual)
- Primary completion
- 6 Apr 2021 (actual)
- Study completion
- 6 Apr 2021 (actual)
- First posted
- 27 Mar 2019 (actual)
- Results
- Posted 15 Jul 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the efficacy of JNJ-70033093 in preventing total venous thromboembolism (VTE) events (proximal and/or distal deep vein thrombosis [DVT] [asymptomatic confirmed by venography assessment or objectively confirmed symptomatic], nonfatal pulmonary embolism [PE], or any death) during the treatment period.
Detailed description
JNJ-70033093 is an oral anticoagulant for prevention and treatment of thromboembolic events (for example, VTE) that binds and inhibits activated form of human coagulation Factor XI (FXIa) with high affinity and selectivity. The study will consist of 3 phases: up to 30-day screening phase before total knee replacement (TKR) surgery, 10 to14 day postoperative dosing phase, and 4-week follow-up phase. The hypothesis of this study is JNJ-70033093 reduces risk of total VTE during treatment period. The total duration of participation following randomization will be approximately 6 weeks. Efficacy evaluations include unilateral venography assessment of operated leg and assessments of symptomatic DVT, PE, or death. Safety evaluation includes adverse events, clinical laboratory tests, and physical examinations. The safety and efficacy will be monitored throughout the study.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Group A: JNJ-70033093 25 mg + Placebo BID | Experimental | Drug: JNJ-70033093 25 mg, Drug: PlaceboParticipants will receive JNJ-70033093 25 milligram (mg) (1*25 mg capsule) and 1 placebo capsule twice daily (BID), orally for 10 to 14 postoperative days. |
| Group B: JNJ-70033093 50 mg BID | Experimental | Drug: JNJ-70033093 50 mgParticipants will receive JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days. |
| Group C: JNJ-70033093 100 mg + Placebo BID | Experimental | Drug: JNJ-70033093 100 mg, Drug: PlaceboParticipants will receive JNJ-70033093 100 mg (1*100 mg capsule) and 1 placebo capsule BID orally for 10 to 14 postoperative days. |
| Group D: JNJ-70033093 200 mg BID | Experimental | Drug: JNJ-70033093 200 mgParticipants will receive JNJ-70033093 200 mg (2*100 mg capsules) BID orally for 10 to 14 postoperative days. |
| Group E: JNJ-70033093 25 mg Once Daily + Placebo | Experimental | Drug: JNJ-70033093 25 mg, Drug: PlaceboParticipants will receive JNJ-70033093 25 mg (1*25 mg capsule) once daily and 1 placebo capsule in the morning and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. |
| Group F: JNJ-70033093 200 mg Once Daily + Placebo | Experimental | Drug: JNJ-70033093 200 mg, Drug: PlaceboParticipants will receive JNJ-70033093 200 mg (2*100 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. |
| Group G: JNJ-70033093 50 mg once daily + Placebo | Experimental | Drug: JNJ-70033093 50 mg, Drug: PlaceboParticipants will receive JNJ-70033093 50 mg (2*25 mg capsules in the morning) once daily and 2 placebo capsules in the evening, orally for 10 to 14 postoperative days. |
| Group I: Enoxaparin 40 mg Once Daily | Active comparator | Drug: Enoxaparin 40 mgParticipants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Medically stable and appropriate for anticoagulant prophylaxis as determined by the investigator on the basis of physical examination, medical history, and vital signs performed as part of screening for elective total knee replacement (TKR) surgery
- Medically stable and appropriate for anticoagulant prophylaxis on the basis of clinical laboratory tests performed as part of local standard-of-care as part of screening for elective TKR surgery
- Has plans to undergo an elective primary unilateral TKR surgery
- A woman must be- a) Not of childbearing potential; b) Of childbearing potential and practicing a highly effective method of contraception (failure rate of less than [<]1 percent [%] per year when used consistently and correctly) and agrees to remain on a highly effective method for the duration of study drug with JNJ-70033093 plus 5 half-lives of study drug plus 30 days (duration of ovulatory cycle) for a total of 34 days after the completion of treatment, pregnancy testing (serum or urine) prior to the first dose of study drug
- Willing and able to adhere to the lifestyle restrictions specified in this protocol
Key exclusion criteria (5 listed)
- History of any condition for which the use of low molecular-weight heparin (LMWH) is not recommended in the opinion of the investigator (for example, previous allergic reaction, creatinine clearance <30 milliliter per minute [mL/minute])
- History of severe hepatic impairment
- Planned bilateral revision or unicompartmental procedure
- Unable to undergo venography (for example, due to contrast agent allergy, poor venous access, or impaired renal function that would increase the risk of contrast-induced nephropathy
- Known previous pulmonary embolism (PE) or deep vein thrombosis (DVT) in either lower extremity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| JNJ-70033093 25 mgAlso: BMS-986177Participants will receive JNJ-70033093 25 mg (1*25 mg capsule) BID (in Group A) or once daily (in Group E), orally for 10 to 14 postoperative days. | Drug | Group A: JNJ-70033093 25 mg + Placebo BID, Group E: JNJ-70033093 25 mg Once Daily + Placebo |
| JNJ-70033093 50 mgAlso: BMS-986177Participants will receive JNJ-70033093 50 mg (2*25 mg capsules) BID orally for 10 to 14 postoperative days. | Drug | Group B: JNJ-70033093 50 mg BID, Group G: JNJ-70033093 50 mg once daily + Placebo |
| JNJ-70033093 100 mgAlso: BMS-986177Participants will receive JNJ-70033093 100 mg (1*100 mg capsule) BID, orally for 10 to 14 postoperative days. | Drug | Group C: JNJ-70033093 100 mg + Placebo BID |
| JNJ-70033093 200 mgAlso: BMS-986177Participants will receive JNJ-70033093 200 mg (2*100 mg capsules) BID (in Group D) or once daily (in Group F), orally for 10 to 14 postoperative days. | Drug | Group D: JNJ-70033093 200 mg BID, Group F: JNJ-70033093 200 mg Once Daily + Placebo |
| PlaceboParticipants will receive placebo matching to JNJ-70033093, orally. | Drug | Group A: JNJ-70033093 25 mg + Placebo BID, Group C: JNJ-70033093 100 mg + Placebo BID, Group E: JNJ-70033093 25 mg Once Daily + Placebo, Group F: JNJ-70033093 200 mg Once Daily + Placebo, Group G: JNJ-70033093 50 mg once daily + Placebo |
| Enoxaparin 40 mgParticipants will receive enoxaparin 40 mg once daily subcutaneously for 10 to 14 postoperative days. | Drug | Group I: Enoxaparin 40 mg Once Daily |
Primary outcome
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated)
Time frame: Up to Day 14
Total VTE was defined as the composite of clinical events committee (CEC)-adjudicated proximal and/or distal Deep Vein Thrombosis (DVT) (asymptomatic confirmed by venography assessment of the operated leg or objectively confirmed symptomatic), nonfatal pulmonary embolism (PE), or any death.
29 secondary outcomes
Number of Participants With Any Bleeding Event (CEC-adjudicated)
Time frame: Up to Day 14; Up to Day 52
Number of Participants With Total VTE (CEC-adjudicated)
Time frame: Up to Day 52
Number of Participants With Composite of Major and Clinically Relevant Nonmajor Bleeding (CRNM) Events (CEC-adjudicated)
Time frame: Up to Day 14, Up to Day 52
Number of Participants With Major Bleeding Events (CEC-adjudicated)
Time frame: Up to Day 14; Up to Day 52
Number of Participants With CRNM Bleeding Events (CEC-adjudicated)
Time frame: Up to Day 14; Up to Day 52
Number of Participants With Minimal Bleeding Events (CEC-adjudicated)
Time frame: Up to Day 14; Up to Day 52
Number of Participants With Major or CRNM Bleeding Events (CEC-adjudicated)
Time frame: Up to Day 14; Up to Day 52
Number of Participants With Major VTE (CEC-adjudicated)
Time frame: Up to Day 52
Number of Participants With Major VTE (CEC-adjudicated)
Time frame: Up to Day 14
Number of Participants With Proximal Deep Vein Thrombosis (DVT) (CEC-adjudicated)
Time frame: Up to Day 14
Number of Participants With Proximal DVT (CEC-adjudicated)
Time frame: Up to Day 52
Number of Participants With Distal DVT (CEC-adjudicated)
Time frame: Up to Day 14
Number of Participants With Distal DVT (CEC-adjudicated)
Time frame: Up to Day 52
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Time frame: Up to Day 14
Number of Participants With Nonfatal Pulmonary Embolism (PE) (CEC-adjudicated)
Time frame: Up to Day 52
Number of Participants With Deaths (CEC-adjudicated)
Time frame: Up to Day 14
Number of Participants With Deaths (CEC-adjudicated)
Time frame: Up to Day 52
Apparent Clearance (CL/F) of JNJ-70033093
Time frame: Up to Day 14
Apparent Volume of Distribution (V/F) of JNJ-70033093
Time frame: Up to Day 14
Impact of Selected Demographics: Apparent Clearance (CL/F) Based on Sex
Time frame: Up to Day 14
Impact of Selected Demographic: Age on CL/F
Time frame: Up to Day 14
Impact of Selected Demographic: Weight on CL/F
Time frame: Up to Day 14
Impact of Selected Laboratory Values: Renal Function on CL/F
Time frame: Up to Day 14
Impact of Selected Demographics: Sex on Apparent Volume of Distribution (V/F)
Time frame: Up to Day 14
Impact of Selected Demographics : Age on V/F
Time frame: Up to Day 14
Impact of Selected Demographics : Weight on V/F
Time frame: Up to Day 14
Impact of Selected Laboratory Values: Renal Function on V/F
Time frame: Up to Day 14
Trend Test for Primary Efficacy Event Rate (CEC Adjudicated) by Multiple Comparison Procedure - Modelling (MCP-Mod) Approach
Time frame: Up to 14 days
Trend Test for the Composite of On-Treatment Major and Clinically Relevant Nonmajor Bleeding (CEC Adjudicated) by MCP-Mod Approach
Time frame: Up to 14 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38038437Whiteson HZ, Frishman WH. Factor XI/XIa Inhibitors: A New Approach to Anticoagulation. Cardiol Rev. 2025 Jul-Aug 01;33(4):306-311. doi: 10.1097/CRD.0000000000000624. Epub 2023 Dec 1.
- Derived from this study: PubMed 34780683Weitz JI, Strony J, Ageno W, Gailani D, Hylek EM, Lassen MR, Mahaffey KW, Notani RS, Roberts R, Segers A, Raskob GE; AXIOMATIC-TKR Investigators. Milvexian for the Prevention of Venous Thromboembolism. N Engl J Med. 2021 Dec 2;385(23):2161-2172. doi: 10.1056/NEJMoa2113194. Epub 2021 Nov 15.
- Individual participant dataSharing planned: Yes. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
117 sites in 18 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing JNJ-70033093 25 mg, JNJ-70033093 50 mg and JNJ-70033093 100 mg in people with Arthroplasty, Replacement, Knee, run by Janssen Research & Development, LLC at 117 sites in 18 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 117 sites in Japan, Spain, United States, Poland, Hungary and 13 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jul 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Total Venous Thromboembolism (VTE) (CEC-adjudicated) (time frame: Up to Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03891524, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.